From the Department of Anaesthesia and Intensive Care (FA, AldL, RA) and Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden (AM).
Eur J Anaesthesiol. 2018 Mar;35(3):165-172. doi: 10.1097/EJA.0000000000000711.
BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo. DESIGN: Randomised, placebo-controlled cross-over study. SETTING: Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014. PARTICIPANTS: Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials. INTERVENTIONS: At separate study sessions, participants received interventions: esmolol (0.7 mg kg bolus over 1 min followed by infusion at 10 μg kg min); 0.9% normal saline bolus then remifentanil infusion at 0.2 μg kg min and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min. MAIN OUTCOME MEASURES: Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively. RESULTS: Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (-1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference -3.1 (95% confidence interval (-4.4 to -1.8)), P < 0.001]. Side-effects were seen with remifentanil but not with esmolol. CONCLUSION: No direct analgesic effect of esmolol could be demonstrated in the present study. The postoperative opioid-sparing effect demonstrated in previous studies, could therefore be secondary to other factors such as avoidance of opioid-induced hyperalgesia, synergy with coadministered opioids or altered pharmacokinetics of those drugs. TRIAL REGISTRATION: European clinical trials database, https://eudract.ema.europa.eu/, EudraCT no. 2011-005780-24.
背景:艾司洛尔可能会减弱疼痛引起的交感神经反应,减少术后阿片类药物的消耗。目前尚不清楚艾司洛尔本身是否具有镇痛作用。
目的:本研究旨在评估艾司洛尔在没有麻醉和阿片类药物的情况下的镇痛效果。我们假设艾司洛尔可将冷加压试验(CPT)中感知到的最大疼痛强度降低 2 分,疼痛评分范围为 0 到 10 的数字疼痛评分量表(NRS)与安慰剂相比。
设计:随机、安慰剂对照交叉研究。
地点:于厄勒布鲁大学医院的术后恢复区。研究时间为 2013 年 11 月至 2014 年 2 月。
参与者:14 名健康志愿者。排除标准包括正在服用药物、怀孕和哺乳以及参加其他医学试验。
干预措施:在单独的研究中,参与者接受以下干预措施:艾司洛尔(0.7mg/kg 推注 1 分钟,然后以 10μg/kg/min 的速度输注);0.9%生理盐水推注,然后瑞芬太尼输注 0.2μg/kg/min,以及 0.9%生理盐水推注和输注,均按照随机顺序进行。所有输注均在 30 分钟内完成。
主要观察指标:CPT 期间感知的最大疼痛强度评分、疼痛耐受度和血流动力学变化,以及与安慰剂相比,分别比较各干预措施的不良反应发生率。
结果:艾司洛尔并未降低 CPT 期间的感知疼痛强度或疼痛耐受度。NRS-max 评分在艾司洛尔组为 8.5(±1.4),安慰剂组为 8.4(±1.3)。平均差值为 0.1[95%置信区间(-1.2 至 1.4)],P 值等于 0.83。瑞芬太尼显著降低 NRS-max 评分,为 5.4(±2.1),与安慰剂相比[平均差值-3.1(95%置信区间(-4.4 至-1.8))],P 值<0.001。瑞芬太尼出现了不良反应,但艾司洛尔没有。
结论:在本研究中未发现艾司洛尔的直接镇痛作用。先前研究中观察到的术后阿片类药物节约作用,可能是由于其他因素引起的,如避免阿片类药物引起的痛觉过敏、与同时给予的阿片类药物的协同作用或这些药物的药代动力学改变。
试验注册:欧洲临床试验数据库,https://eudract.ema.europa.eu/,EudraCT 编号 2011-005780-24。
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